MLCC 2019 | 1

Organised by:

PROGRAMME BOOKLET

1 – 2 March 2019 | Mandarin Orchard Singapore

4TH MULTIDISCIPLINARY LUNG CANCER CONFERENCE

www.mlcc.com.sg

B | MLCC 2019

ContentsWelcome Message

Committees

Invited Faculty

Conference Information

Floor Plan

Scientific Programme

Lecture Abstract

Poster Abstracts

Organisers

Acknowledgement

1

2

3

10

12

13

17

20

26

27

MLCC 2019 | 1

Dear Friends,

On behalf of the Lung Cancer Consortium Singapore and the Local Organizing Committee, it gives us great pleasure to welcome you to the Multidisciplinary Lung Cancer Conference (MLCC 2019), Singapore.

This year’s theme, “United Together in Fighting Lung Cancer”, aims to highlight how major scientific discoveries and technology developments are rapidly transitioning to the clinic and keep participants informed of the latest updates in the preclinical and clinical aspects of the ever-evolving field. Building on the success of the previous conferences, international and national speakers will gather to discuss the science and advances in the treatment and prevention as well as the multidisciplinary management of lung cancer and thoracic malignancies.

Throughout the two days, you will be involved in an enriching learning experience and abundance of networking opportunities. Key topics include lung cancer screening, cancer genomics, as well as novel diagnostics and therapeutics including immunotherapy.

We encourage physicians, scientists, healthcare professionals and researchers in the lung cancer field and anyone interested in thoracic oncology to participate in this conference. It is only through sharing of expertise and fostering of stronger partnerships that we can improve care for our patients.

We hope that this event will serve as a platform to facilitate active scientific exchange and forge networks for future collaborations.

We would like to take this opportunity to thank our faculty for spending their valuable time with us.We hope that you will join our local and international experts from 1st to 2nd March 2019 for an exciting and intellectually stimulating meeting, and that you will take time to enjoy our garden city as well!

Welcome Message

Dr Ross SOOChairmanOrganising Committee

Dr Daniel TAN Co-Chairman Organising Committee

Dr TOH Chee KeongCo-Chairman, Organising CommitteeChairman, Lung Cancer Consortium Singapore

2 | MLCC 2019

CommitteesLOCAL ORGANIZING AND SCIENTIFIC COMMITTEE

Chairman Dr Ross SOO

Co-Chairman Dr TOH Chee Keong

Co-Chairman Dr Daniel TAN

Scientific Committee Dr Anuradha THIAGARAJAN Dr HUANG Yiqing

Dr Amit JAIN A/Prof LEE Pyng

Dr Darren LIM Dr ONG Boon Hean

Dr Jens SAMOL Dr Anders SKANDERUP

Dr TAN Eng Huat Dr TAN Wan Ling

Dr Ivan THAM Dr TOO Chow Wei

Dr Joe YEONG

Secretariat Ms WANG Lanying

MLCC 2019 | 3

OVERSEAS FACULTY

Invited Faculty

Professor Raphael BUENOChief, Division of Thoracic Surgery, Brigham and Women’s Hospital Professor of Surgery, Harvard Medical SchoolBoston, USA

Dr Marina GARASSINOChief of Medical Thoracic Oncology UnitDepartment of Medical Oncology and HematologyFondazione IRCCS Istituto Nazionale dei Tumori di MilanoMilan, Italy

Professor Ming TSAOConsultant Pathologist and Senior ScientistUniversity Health Network, Princess Margaret Cancer CentreProfessor of Laboratory Medicine and PathobiologyProfessor of Medical BiophysicsUniversity of TorontoToronto, Ontario, Canada

Professor Tony MOKProfessor and ChairmanDepartment of Clinical OncologyChinese University of Hong KongHong Kong

Professor Sai-Hong Ignatius OUHealth Science Clinical ProfessorChao Family Comprehensive Cancer CenterDepartment of Medicine, Division of Hematology-OncologyUniversity of California Irvine School of Medicine Orange, CA, USA

Dr Sanjay POPATConsultant Medical Oncologist,Royal Marsden HospitalUnited Kingdom

4 | MLCC 2019

LOCAL FACULTYDr Dokev Basheer Ahmed Aneez AHMEDHead of Service, Senior ConsultantDepartment of General SurgeryTan Tock Seng Hospital

Professor ZHOU CaicunDepartment of Medical OncologyShanghai Pulmonary HospitalTongji University China

Dr ANG Mei-KimSenior ConsultantSingHealth Duke-NUS Lung CentreSenior ConsultantDivision of Medical OncologyNational Cancer Centre Singapore

Dr Yvonne ANGAssociate ConsultantNCIS - Department of Haematology-OncologyNational University Hospital

Dr Atasha ASMATConsultantDivision of Thoracic SurgeryTan Tock Seng Hospital

Associate Professor CHEAH Foong KoonHOD, Department of Cardiac Radiology, National Heart Centre SingaporeSenior Consultant, Department Of Diagnostic Radiology, Singapore General Hospital

MLCC 2019 | 5

Dr CHIN Tan MinMedical OncologyRaffles Hospital

Dr Kevin CHUA Lee MinConsultantDivision of Radiation OncologyNational Cancer Centre Singapore

Dr Anantham DEVANANDDeputy Head and Senior ConsultantSinghealth Duke-NUS Lung CentreSenior ConsultantRespiratory and Critical Care MedicineSingapore General Hospital

Dr Brett DOBLEAssistant ProfessorLien Centre for Palliative CareProgramme in Health Services and Systems ResearchDuke-NUS Medical School

Dr Amit JAINMedical OncologyNational Cancer Centre Singapore

Dr KOH Wee YaoSenior Consultant Radiation OncologyNational Cancer Institute SingaporeNational University Health System

Dr Gillianne LAIMedical OncologyNational Cancer Centre Singapore

6 | MLCC 2019

Associate Professor LEE PyngSenior ConsultantDivision of Respiratory and Critical Care MedicineNational University Hospital

Dr LEONG Swan SwanMedical Oncology SpecialistGleneagles Hospital

Dr Charlene LIEW Jin YeeConsultantDepartment of Diagnostic RadiologyChangi General Hospital

Dr Harish Mithiran MUTHIAHConsultant Department of Cardiac, Thoracic and Vascular Surgery, NUHCSAssistant Programme Director NUH Cardiothoracic Surgery Residency ProgramNational University Heart Centre Singapore

Mr NG Kwong HoeHead, Evaluation & Appraisal TeamAgency for Care EffectivenessMinistry of Health

Dr ONG Boon HeanService Chief (SGH Campus)SingHealth Duke-NUS Lung CentreConsultantDepartment of Cardiothoracic SurgeryNational Heart Centre Singapore

Dr Brendan PANGConsultant Pathologist and Designee Laboratory Director,Angsana Molecular and Diagnostics Laboratory,Parkway Laboratory Services LtdVisiting Consultant,National University Cancer Institute, Singapore & National University Hospital

MLCC 2019 | 7

Dr PHUA Ghee CheeSenior ConsultantDepartment of Respiratory and Critical MedicineSingapore General Hospital

Dr Jens SAMOLSenior ConsultantDepartment of Medical OncologyTan Tock Seng Hospital

Dr Ross SOOSenior Consultant, Department of Haematology-Oncology, National University Cancer Institute, SingaporeAdjunct Senior Research Fellow, Cancer Science Institute, National University of Singapore

Dr SOO Ing XiangConsultant Thoracic SurgerySingHealth Duke-NUS Lung Centre, Singhealth Department of Cardiothoracic Surgery, National Heart Centre Singapore

Dr SOON Yu YangAssociate ConsultantRadiation OncologyNational University Hospital

Dr Daniel TAN Shao WengSenior ConsultantSingHealth Duke-NUS Lung CentreSenior ConsultantDivision of Medical OncologyNational Cancer Centre Singapore

8 | MLCC 2019

Dr TAN Wan LingAssociate ConsultantSingHealth Duke-NUS Lung CentreConsultantDivision of Medical OncologyNational Cancer Centre SingaporeNational Cancer Centre Singapore

Dr TAN Yew OoMedical Oncology SpecialistIcon SOC Farrer Park Medical Clinic

Dr Melvin TAY Chee Kiang ConsultantDepartment of Respiratory & Critical Care MedicineSingapore General Hospital

Dr Ivan THAMHead and Senior Consultant, Department of Radiation Oncology, National University CancerInstitute, Singapore and NCIS, Tan Tock Seng HospitalAssistant Professor, National University Of SingaporeClinical Director, A*Star Clinical Imaging Research Centre

Dr Anuradha THIAGARAJANConsultantRadiation OncologyNational Cancer Centre Singapore

Associate Professor TAN Soo YongHead, Department of Pathology, National University of Singapore & Chief, Department of Pathology, National University HospitalGroup Director for Pathology, National University Health SystemAssociate Professor, Yong Loo Lin School of Medicine, National University of SingaporeSenior Principal Investigator, Institute of Cell and Molecular Biology (IMCB), A*STARHead, Advanced Molecular Pathology Laboratory, IMCBVisiting Professor, University Malaya, Kuala LumpurVisiting Professor, Guangdong Academy of Medical Sciences and Guangdong Hospital, ChinaSenior Consultant, Regulatory Policy and Licensing Division, Ministry of Health, SingaporeSenior Consultant, Manpower Development and Professional Standards Division, Ministry of Health, Singapore

MLCC 2019 | 9

Dr TOH Chee KeongSenior ConsultantNational Cancer Centre

Dr TOO Chow WeiConsultantVascular and Interventional RadiologySingapore General Hospital

Dr Grace YANGConsultantDivision of Supportive and Palliative CareNational Cancer Centre Singapore

Dr YAP Swee PengSenior ConsultantDivision of Radiation OncologyNational Cancer Centre Singapore

Dr Alethea YEEDivision of Supportive and Palliative CareNational Cancer Centre Singapore

Dr YONG Woon ChaiHead, Dept of Palliative Care, Alexandra HospitalSenior Consultant, National University Cancer Institute, Department of Haematology-Oncology, NUHSVisiting Consultant, St.Luke Hospital

Dr ZENG ZengSenior ScientistA*STAR - Agency for Science, Technology and Research

10 | MLCC 2019

Conference InformationCONFERENCE VENUEMandarin Orchard HotelLevel 6, Grand Mandarin Ballroom333 Orchard Road, Singapore 238867Tel: (+65) 6737 4411, Fax: (+65) 6732 2361Website: http://www.meritushotels.com/en/mandarin-orchard-singapore/index.html

CONFERENCE REGISTRATION COUNTERThe Registration Counter is located at the Foyer Area outside Grand Mandarin Ballroom 2 at Level 6. The counter will be opened daily from 0800 – 1700 hours.

CONFERENCE SATCHEL AND NAME BADGEUpon registration, you will receive a Conference satchel with your name badge. You are required to wear your name badge to all sessions and events. Should you lose your name badge, please contact the Conference Secretariat for a replacement. Please note that replacement fee applies.

EXHIBITIONA state-of-the-art exhibition held by biotech and pharmaceutical companies will be held at Level 6, Mandarin Grand Ballroom from 0800 - 1700 hours on both days.

CME / CPE INFORMATION(Applicable to Singapore registered Healthcare Professionals ONLY)CME / CPE points will be accorded for attending the workshops and main sessions. Delegates are required to sign on the attendance record on a daily basis at the conference registration counter. Delegates are required to sign at the beginning of the day and during lunch time.

LOST AND FOUNDFor lost and found items, please approach the Conference Registration Counter.

CONFERENCE LANGUAGEEnglish is the official language of this conference.

MESSAGE BOARDThere will be a message board next to the Conference Registration Counter. Please check this board regularly for messages.

LIABILITYThe Organisers are not liable for any personal accidents, illnesses, loss or damage to private properties of delegates during the Conference. Delegates are advised to arrange for appropriate insurance coverage during the conference period.

MLCC 2019 | 11

DISCLAIMERWhilst every attempt will be made to ensure that all aspects of the Conference will take place as scheduled, the Organising Committee reserves the right to make appropriate changes should the need arises with or without prior notice.

SPEAKERS’ HOSPITALITY SUITEThe Speakers’ Hospitality Suite is located at Foyer Area outside Mandarin Ballroom at Level 6. All speakers should submit their presentations in Microsoft PowerPoint 2016 or earlier version in a USB Drive, at least 30 minutes prior to their session. Notebooks are also available in the room for editing.

POSTER PRESENTATIONEach presenter will be allocated a poster board (one side only) with an area of 1m x 2m. Each poster board will be marked with a poster panel number. Poster should be set up on Friday, 1 March 2019, between 0800 — 0900 hours and removed on Saturday, 2 March 2019 after 1520 hours.

CONFERENCE SECRETARIATThe Conference Secretariat is located at Level 8, Room 801, during the Conference Period.

12 | MLCC 2019

Floor Plan

Faculty Room

(Foyer area)

Lecture Hall(Ballroom 1 & 2)

Exhibition Posters

Reception Area

(Ballroom 3)

Registration Counter(Foyer area)

MLCC 2019 | 13

Scientific Programme4th Multidisciplinary Lung Cancer Conference

Friday, 1 March – Saturday, 2 March 2019Mandarin Orchard Singapore

Day 1: Friday, 1 March 2019Time Programme Speaker/Chairpersons

0800 – 0900 Registration/Welcome Coffee & Tea

0900 – 0905 Welcome Address Toh Chee Keong

0905 – 0910 Introduction to 4th Multidisciplinary Lung Cancer Conference Ross Soo

0910 – 0950 Keynote Address: The Era of Translational Research Raphael Bueno

0950 – 1110 Session 1: Lung Cancer ScreeningChairpersons:Cheah Foong KoonOng Boon Hean

0950 – 1010 Lung Cancer Screening Charlene Liew

1010 – 1030 Management of Indeterminate Pulmonary Nodule Anantham Devanand

1030 – 1050 Current Directions for Screening in Singapore Toh Chee Keong

1050 – 1110 Imaging: Role of AI for Early Detection Zeng Zeng

1110 – 1200 Morning Tea Symposium (sponsored by Takeda)

1110 – 1200 Updates on the Evolving Landscape of Targeted Therapy in NSCLC Ross Soo

1200 – 1320 Session 2: PathologyChairpersons:Tan Soo YongTan Yew Oo

1200 – 1220 Molecular Testing for NSCLC 2019 Ming Tsao

1220 – 1240 Incorporating Emerging Technologies into the Clinic (Liquid Biopsies, NGS) (sponsored by BMS) Tony Mok

1240 – 1300 Value Driven Health Care in Cancer Ng Kwong Hoe

1300 – 1320 Panel Discussion/Voting Next Generation Sequencing: Ready for prime time?

Brendan Pang, Brett Doble, Daniel Tan, Ming Tsao, Tan Soo Yang, Tan Yew Oo, Tony Mok

14 | MLCC 2019

1320 – 1420 Lunch Symposium (sponsored by Boehringer Ingelheim)

1320 – 1420 Treatment Strategy with EGFR TKIs: A Marathon or a Sprint? Tony Mok

1420 – 1520 Session 3: Early Stage DiseaseChairpersons:Atasha Binti AsmatPhua Ghee Chee

1420 – 1440 Role of Minimally Invasive Techniques (Robotic/VATS) and Sublobar Resections for Early Stage Lung Cancer

Dokev Basheer Ahmed Aneez Ahmed

1440 – 1500 Radiation: SBRT, Radical RT Anuradha Thiagarajan

1500 – 1520 Bronchoscopic Approaches to Early Stage Lung Cancer Melvin Tay Chee Kiang

1520 – 1610 Afternoon Tea Symposium (sponsored by Pfizer)

1520 – 1610 Advances in the Diagnosis and Treatment of ALK-positive NSCLC Ignatius Ou

1610 – 1720 Session 4: Locally Advanced Disease (Stage III Tumor Board)

Chairpersons:Tan Wan LingYap Swee Peng

1610 – 1620 N2 Case Presentation Tan Wei Chong

1620 – 1635 Surgical Oncology Perspective Soo Ing Xiang

1635 – 1650 Radiation Oncology Perspective Ivan Tham

1650 – 1705 Medical Oncology Perspective Ang Mei-Kim

1705 – 1720 Discussion and Q&A

Ang Mei-Kim, Ivan Tham, Soo Ing Xiang, Tan Wan Ling, Tan Wei Chong, Yap Swee Peng

Disclaimer: Whilst every attempt will be made to ensure that all aspects of the programme will take place as scheduled, the Organisers reserve the right to make appropriate changes should the need arise.

MLCC 2019 | 15

Day 2: Saturday, 2 March 2019

Time Programme Speaker

0800 – 0900 Registration

0815 – 0900

Breakfast Symposium (sponsored by Roche) Chairperson: Daniel Tan

Case Presentation Han Shuting, Joshua Hoe, Tan Ya Hwee

Panel Discussion

Brendan Pang, Kevin Chua, Ong Boon Hean, Ross Soo, Soon Yu Yang, Toh Chee Keong

0900 – 1020 Session 5: Updates in Other Thoracic CancersChairpersons:Jens SamolLeong Swan Swan

0900 – 0920 Mesothelioma – Updates Raphael Bueno

0920 – 0940 Thymic Tumours – Updates Sanjay Popat

0940 – 1000 Small Cell Lung Cancers/Large Cell NEC – What’s New Caicun Zhou

1000 – 1020 Panel Discussion

Caicun Zhou, Jens Samol, Leong Swan Swan, Raphael Bueno, Sanjay Popat

1020 – 1110 Morning Tea Symposium (sponsored by Astrazeneca)

1020 – 1110 Experts Perspective on the Management of EGFRm NSCLC: TKI Standard of Care in 2019 Sanjay Popat

1110 – 1230 Session 6: Advanced Stage (I)Chairpersons:Chin Tan MinSoon Yu Yang

1110 – 1130 Role of Surgery in Stage IV Disease with Oligometastasis Harish Mithiran Muthiah

1130 – 1150 Radiation: Role of Radical RT for Oligometastatic Disease Kevin Chua Lee Min

1150 – 1210 Role of Ablation Too Chow Wei

1210 – 1230 Medonco: Oligometastatic Disease – Overview, Definition, Patient Selection for Radical Approaches Caicun Zhou

1230 – 1330 Lunch Symposium (sponsored by Astrazeneca)

1230 – 1330 New Standard of Care in Stage III NSCLC: Pivotal Role of MDT Sanjay Popat

16 | MLCC 2019

1330 – 1430 Session 7: Advanced Stage (II)Chairpersons:Gillianne LaiYvonne Ang

1330 – 1350 Medonco: Immunology Landscape in Metastatic NSCLC Marina Garassino

1350 – 1410 Oncogene-Driven Tumours - Updates Ignatius Ou

1410 – 1430 Rationale for Combinatorial Strategies in Advanced NSCLC Ross Soo

1430 – 1520 Afternoon Tea Symposium (sponsored by MSD) Chairperson: Ross Soo

1430 – 1520 Breaking Frontiers in Advanced NSCLC with Immuno-Oncology Marina Garassino

1520 – 1640 Session 8: Palliative/Supportive careChairpersons:Alethea YeeYong Woon Chai

1520 – 1540 Palliative Care: Optimal Time to Start Palliative Care Grace Yang

1540 – 1600 Radiation: Management of CNS Mets (SRS, WBRT) Koh Wee Yao

1600 – 1620 Bronchoscopic/Pleural Interventions for Palliation Lee Pyng

1620 – 1640 IO Toxicities Amit Jain

1640 – 1650 Best Poster Award Toh Chee Keong

1650 Closing Remarks Daniel Tan

Disclaimer: Whilst every attempt will be made to ensure that all aspects of the programme will take place as scheduled, the Organisers reserve the right to make appropriate changes should the need arise.

MLCC 2019 | 17

Lecture AbstractsSESSION I – LUNG CANCER SCREENINGLung Cancer ScreeningDr Charlene Liew

Lung cancer is the number one cancer killer in Singapore and in the world. Despite advances in imaging techniques and treatment, the prognosis remains poor. CT Lung cancer screening was shown to reduce cancer deaths in the USA by 20% and yet more evidence has surfaced since the landmark NLST study in 2011. What are the unique challenges that we face in Singapore to build a successful lung cancer screening program? Dr Charlene Liew is the lead author of the Singapore College of Radiologists’ Position Paper on CT lung cancer screening. Follow her as we take a deep dive into the challenges and promise of CT Lung cancer screening in Singapore.

Management of Indeterminate Pulmonary NoduleDr Anantham Devanand

Lung nodules can be classified as solid, nonsolid and part solid. A guideline based approach to dealing with nodules may result in fewer investigations and complications. Nodules that are under 8 mm are managed according to size criteria and the frequency of radiological surveillance in determined by the risk profile in solid nodules; and the solid components in part solid nodules.

Nodules that are greater than 8 mm are profiled according to the risk of malignancy. The surgical risks of the patient and the need for certainty in diagnosis determine the thresholds for surgical intervention or continued radiological surveillance. The patients in between those thresholds are subject to either PET scanning or a minimally invasive biopsy.

The data on diagnostic yield for CT-guided transthoracic biopsy of peripheral lung nodules exceeds 90% and is superior in meta-analysis to a bronchoscopic approach. However, there remain concerns of pneumothorax and pleural seeding as complications. New bronchoscopic technology has attempted to close the gap with CT-guided transthoracic biopsy. This has focused on improved pre-procedure planning, endoscopic navigation, real-time localization and on-site evaluation of histology. Despite the advances, these bronchoscopic approaches have not matched CT-guided biopsy yields yet. This has spurred the used of a combination of bronchoscopic technologies.

Asian cancer patients have certain characteristics: they are younger, have more non-smokers and have more driver oncogenic mutations like EGFR. Therefore, traditional risk calculators developed in non-Asian patients fail to provide accurate predictions. PET scans should also be used carefully because of high prevalence of false positives (granulomatous disease) and false negatives (adenocarcinoma in situ). Longer periods (> 3 years) of radiological surveillance should be considered in nonsolid nodules because of the long doubling times involved. These are some of concerns that have been highlighted in the Asian guidelines for the management of lung nodules.

18 | MLCC 2019

SESSION 2 - PATHOLOGY

Molecular Testing for NSCLC 2019Professor Ming Tsao

Testing for predictive biomarkers is now an integral part of routine pathology diagnosis for non-small cell lung cancer (NSCLC). These biomarkers are essential for personalizing the treatment of advanced NSCLC patients with targeted and immune therapies. Currently required tests include EGFR mutations, ALK and ROS-1 gene rearrangement or their fusion protein expression, BRAF V600E mutation, and PD-L1. Depending on the marker, testing is performed using molecular techniques (e.g. PCR, RT-PCR or nucleotide sequence analysis), immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), or next generation sequencing (NGS). In 2013, the College of American Pathologists (CAP) in collaboration with International Association for the Study of Lung Cancer (IASLC) and Association of Molecular Pathologists (AMP), published a guideline that sets out basic principles of molecular testing in lung cancer. This guideline mainly focused on EGFR and ALK testing. Testing can be done reliably on DNA isolated from formalin-fixed paraffin embedded (FFPE) tissue, but prolonged atmospheric exposure (>2-4 months) of unstained sections may compromise test efficiency for PCR, FISH and IHC. Testing on tissue that has been exposed to acid decalcifying solution is also discouraged. The guideline recommended that EGFR and ALK are tested on all advanced stage patients with lung adenocarcinoma (ADC) and NSCLC with ADC component, and clinical factors should not be used to select patients for testing. Testing on archival, primary or metastatic lesions and cytology materials are equally acceptable, and testing should be completed in less than 10 working days after the receipt of tissue materials by the testing laboratory. In 2018, CAP/IASLC/AMP updated the guideline, which reaffirmed most of the 2013 recommendations on EGFR testing but expanded to include testing mutations on exons 18-21 with at least 1% prevalence. ALK IHC and RT-PCR were considered diagnostic tests equivalent to FISH. In addition, ROS-1 was recommended as routine test like EGFR and ALK. It was recommended that testing of additional low prevalence driver oncogenes (e.g., BRAF V600E, MET exon-14, HER2, RET, NTRK, etc) be performed by multiplex sequencing panels. The 2018 guideline also recommended that EGFR-mutant lung cancer patients who progress on first/second generation EGFR TKI be tested for T790M mutation, as T790M+ patients are eligible for treatment with osimertinib, the 3rd generation EGFR TKI. In this setting, re-biopsy of growing tumor is the reference standard, but cell-free plasma DNA testing for T790M has rapidly gained favor for initial T790M testing, with re-biopsy reserved for blood test negative patients. The latter is important as sensitivity of plasma T790M test is only 70%, and some patients progress due to small cell transformation, which can only be diagnosed by histopathology. Aside from testing for driver oncogenes, testing PD-L1 expression level by IHC has become a standard for first line monotherapy with pembrolizumab, an anti-PD1 immune checkpoint inhibitor. As more tests are required for treatment decision, pathologists need to develop strategy that provide not only accurate diagnosis, but also molecular testing results using limited tissue materials and shortest possible turn-around time.

MLCC 2019 | 19

SESSION 8 – PALLIATIVE/SUPPORTIVE CAREPalliative Care: Optimal Time to Start Palliative CareDr Grace Yang

The call to start palliative care early can be heard throughout the world. When is the optimal time? Well, it depends on what you mean by “palliative care”. This lecture will introduce the various forms and functions of palliative care.

Radiation: Management of CNS Mets (SRS, WBRT)Dr Koh Wee Yao

The natural history of lung cancer is one of frequent metastasis to the brain and used to signify that patients are terminal with median survival of 3 months from that event. However, the face of lung cancer has changed significantly over the years and many more patients are surviving for a longer time despite having metastatic lung cancer to the brain. WE discuss the nuances of the various radiotherapy options for brain metastases from lung cancer.

20 | MLCC 2019

Poster AbstractsA PHASE II WITH A LEAD-IN PHASE I STUDY TO EXAMINE SAFETY AND EFFICACY OF HYDROXYCHLOROQUINE AND GEFITINIB IN ADVANCED NSCLC

Yiqing Huang1, Alvin SC Wong1, Ross Andrew Soo1, Thomas IP Soh1, Angela SL Pang1, Chee Seng Tan1, Winnie HY Ling1, Pei Jye Voon1, Joline SJ Lim1, Raghav Sundar1, Nesaretnam Kumarakulasinghe1, Hong Liang Lim1, Boon Cher Goh1,2, Tan Min Chin1,2

1 Department of Haematology-Oncology, National University Cancer Institute, Singapore; 2 Cancer Science Institute, Singapore

Introduction:Preclinical work demonstrated re-sensitization of cells to EGFR TKIs with erlotinib and hydroxychloroquine (HCQ) combination after acquired resistance. We examine the safety and efficacy of HCQ with gefitinib in an Asian cohort of NSCLC patients.

Method:We enrolled stage IIIB/IV lung adenocarcinomas with sensitizing EGFR mutations. In early phase of the study, non-smokers with unknown EGFR status were allowed. For the phase I lead-in study (Nov 2008-Jan 2010), maximum tolerable dose (MTD) of HCQ and gefitinib was ascertained using 3+3 dose escalation schema.

In the phase II single-arm study (March 2010-May 2016), patients were treated with gefitinib and MTD of HCQ, and stratified into TKI-naïve and TKI-treated cohorts. Primary end point in both cohorts were objective response rates (ORR) and progression-free survival (PFS).

Results:75 patients were treated. EGFR mutations were identified in 77.3%. In the phase I cohort (n=13), MTD of HCQ was 600mg om. HCQ-gefitinib combination was well-tolerated. Common adverse events were rash and diarrhea, mainly from gefitinib. There was no dose-limiting toxicity. In TKI-naïve cohort (n=37) of the phase II study, ORR was 75.8% (95% CI 57.7-88.9). Median PFS was 9.4 months (95% CI 6.8-12.0). Four patients had early toxicities, including pneumonitis and hepatitis flare. In the TKI-treated cohort (n=25), disease control rate with TKI re-challenge was 50% (95% CI 21.9-70.9), ORR was 4.2% (95% CI 0.1-21.1). Median PFS was 2.4months, and median overall survival was 9.9months (95% CI 5.7-14.0). Three patients achieved PFS exceeding 7 months after re-challenge (7.6; 11.2; 15.9 months).

Conclusion: Combination of HCQ-gefitinib is safe. In TKI-naïve cohort, combination treatment did not improve PFS over reported average of 10 months for 1st-generation EGFR TKIs. However, in the TKI-treated cohort, re-responses and disease control were seen, suggesting either a re-treatment effect or disease stabilization with addition of HCQ in acquired EGFR resistance.

MLCC 2019 | 21

ASSOCIATION BETWEEN RADIATION HEART DOSIMETRIC PARAMETERS, MYOCARDIAL INFARCT AND OVERALL SURVIVAL IN STAGE III NON-SMALL CELL LUNG CANCER TREATED WITH DEFINITIVE THORACIC RADIOTHERAPY

Chia Ching Lee1, Huili Zheng2, Yu Yang Soon1, Ling Li Foo2, Wee Yao Koh1, Cheng Nang Leong1, Balamurugan Vellayappan1, Jeremy Chee Seong Tey1, Ivan Weng Keong Tham1

1 Department of Radiation Oncology, National University Cancer Institute, Singapore; National University Hospital, Singapore2 National Registry of Disease Office, Research & Surveillance Division, Health Promotion Board, Singapore

Introduction:The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy.

Methods: We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analyses to assess the association between various RHDPs, AMI and OS. Results:120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60Gy. Median mean heart dose (MHD) was 12.6Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01 – 1.06; P= 0.008) and volume of heart receiving at least 5Gy (V5) (HR, 1.01; 95% CI, 1.00 – 1.03; P= 0.042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. Conclusions:The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. Based on our findings, there is insufficient evidence to conclude that RHDPs are associated with AMI or OS.

22 | MLCC 2019

BENEFIT OF OSIMERTINIB IN ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS WITH LOW LEVEL T790M EXPRESSION ON PLASMA-BASED DROPLET DIGITAL PCR (DDPCR) AFTER PROGRESSION ON FIRST- OR SECOND-GENERATION EGFR-TKIS

Elise Vong1, Liuh Ling Goh2, Alex Yuan Chi Chang3, Siew Wei Wong4

1,3,4 Department of Medical Oncology, Tan Tock Seng Hospital, Singapore2 Molecular Diagnostic Laboratory, Tan Tock Seng Hospital, Singapore

Background:After progression on first- or second-generation EGFR-TKIs in advanced NSCLC, osimertinib shows potent activity in patients with tissue T790M mutation detected based on the cobas EGFR Mutation Test (Roche Molecular Systems)1, which has a tissue T790M limit of detection (LOD) of 2-3%2. The cobas test is also currently the only FDA-approved plasma-based EGFR assay, with a T790M detection sensitivity of 60-70% compared to tissue-based testing.3 Newer highly sensitive quantitative tests such as ddPCR (Bio-Rad) have a T790M LOD of <1% and plasma sensitivity of 70-90%.3 However, there is currently no established T790M cut-off for quantitative assays that predicts response to osimertinib. This study aims to evaluate the objective response rate (ORR) to osimertinib amongst patients with low level T790M-positivity on plasma-based ddPCR, in whom the optimum treatment (i.e. osimertinib or chemotherapy) is unclear.

Methods:We conducted a retrospective chart review of patients from our institution from September 2016 to October 2018 with EGFR-mutated advanced NSCLC who were T790M-positive at ≤3% mutant abundance on plasma-based ddPCR testing after disease progression following first- or second-generation EGFR TKI, and who received osimertinib.

Results:12 patients were identified and included in the analysis. 10/12 patients had received as systemic treatment only 1 line of EGFR-TKI. The T790M mutant abundance ranged from 0.03-3% (median 1%). ORR based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) was 50% (6/12 patients). 3 patients had stable disease and 3 had radiological and/or clinical disease progression. Amongst patients with plasma T790M levels of ≤1%, 1.1-2%, and 2.1-3%, 3/6, 1/3 and 2/3 patients demonstrated objective responses respectively. The median progression-free survival was 6 months (1-not reached). The duration of treatment at time of data cut-off ranged from 1-18 months, with 4/12 patients still receiving osimertinib.

Conclusion:Our study demonstrates that patients with low level T790M-positivity on plasma-based ddPCR after progression on first- or second-generation EGFR-TKIs derive benefit from osimertinib, and warrants prospective clinical trials to validate our results. 1 Mok et al, N Engl J Med. 2016;376:629–6402 cobas EGFR Mutation Test v2, www.accessdata.fda.gov/cdrh_docs/pdf12/P120019S007c.pdf 3 Sacher et al, J Thorac Oncol. 2017 Sep;12(9):1344-1356

MLCC 2019 | 23

DISCORDANCE IN EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION BETWEEN PRIMARY AND METASTATIC TUMOURS IN NON-SMALL-CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Chia Ching Lee1, Yu Yang Soon1, Wee Yao Koh1, Cheng Nang Leong1, Jeremy Chee Seong Tey1, Ivan Weng Keong Tham1

1 Department of Radiation Oncology, National University Cancer Institute, Singapore; National University Hospital, Singapore; National University Health System, Singapore; National University Singapore, Singapore

Objective:To determine the frequency of discordance in epidermal growth factor receptor (EGFR) mutation between primary and metastatic tumours in non-small-cell lung cancer (NSCLC).

Methods:We searched MEDLINE and EMBASE database for eligible studies. We calculated the percentages of discordance in EGFR mutation status and 95% confidence intervals (CIs) for each study. We performed subgroup analyses for EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis relative to diagnosis of primary tumor (synchronous or metachronous). We used the random effects model to calculate the pooled percentage. Heterogeneity across studies was assessed using the I squared (I2) statistic method. Comparisons of subgroups was performed using chi-square test.

Results:We identified 19 eligible studies including 552 patients. The overall discordance rate in EGFR mutation status was 11.53% (95% CI= 5.32% to 19.71%; I2 = 82.57%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI=14.13 to 79.02) than central nervous system (15.41%, 95% CI= 5.86 to 28.42; P < 0.001) and lung/ pleural metastases (11.68, 95% CI= 7.93 to 16.05; P < 0.001). Subgroup analyses did not show any significant effect modification on the discordance rates by the EGFR mutation status (mutant, 18.74%; wildtype,13.92%, P= 0.140), methods of testing (direct sequencing, 13.52%; allele-specific testing, 18.62%; P= 0.115) or timing of metastasis relative to diagnosis of primary tumor (synchronous, 14.83%; metachronous, 15.14%; P= 0.760).

Conclusions:The discordance rates in EGFR mutation status between primary NSCLC and distant metastatic tumors varied largely between studies. Discordance occurred more commonly in bone compared with brain and lung/ pleural metastatic sites. Future researches assessing the impact of EGFR mutation discordance on treatment efficacy and survival are required.

24 | MLCC 2019

IMPACT OF RADIATION THERAPY QUALITY ASSURANCE ON ESTIMATES OF INTERVENTION EFFECTS ON PROGRESSION-FREE AND OVERALL SURVIVAL IN RANDOMIZED TRIALS OF LUNG CANCER TREATED WITH CURATIVE INTENT THORACIC RADIATION THERAPY: A META-EPIDEMIOLOGIC STUDY

Soon YY1, Tan ALZ2, Ng IWS1, Tan TH1, Tey JCS1

1 Deparment of Radiation Oncology, National University Hospital, Singapore2 Department of Preventive Medicine, National University Hospital, Singapore

Background:To evaluate if the estimates of treatment effect differ between randomized trials (RCTs) that reported radiation therapy quality assurance (RTQA) and RCTs, which did not report RTQA, for treatment of lung cancer (LC) using curative intent thoracic radiation therapy (TRT).

Materials and Methods:We searched MEDLINE for eligible meta-analyses (MAs) of RCTs of LC. For each trial in the selected MAs, we reviewed if RTQA was performed and extracted the hazard ratios (HR) with 95% confidence interval (CI) for progression-free (PFS) and overall survival (OS). We quantify the differences in the estimated intervention effect on PFS and OS by a ratio of HRs (rHRs): the HR for trials that performed RTQA to that of trials that did not perform or report RTQA. An rHR more than 1 would indicate a larger HR for trials that performed RTQA compared to trials that did not perform or report. We estimated a combined rHR across MAs using a random effects MA model. We performed a meta-regression analysis to adjust for potential confounders including cancer type, comparisons type, sample size and single-vs-multi center trial .

Results:We included six MAs that comprised of six comparisons and 50 RCTs (22 reported RTQA; 28 did not). Trials that performed RTQA showed similar intervention effect on PFS (rHR 0.96, 95% CI 0.82 to 1.12, P value (P) = 0.57, I squared (I2) = 0%) and OS (rHR 1.00, 95% CI 0.88 to 1.15, P = 0.94, I2 = 0%) compared to trials that did not perform or report RTQA, with low heterogeneity across individual MAs. There was no significant change in the summary rHRs after adjusting for potential confounders.

Conclusions:The conduct of RTQA did not modify the estimates of intervention effects on progression-free and overall survival in randomized trials of lung cancer treated with curative intent thoracic radiation therapy.

MLCC 2019 | 25

LUNG CANCER SURVIVORS: WHAT ARE THEIR CONCERNS?

G.P. Chua MN, Q.S. Ng MD, H.K. Tan FRCSEd, W.S. Ong MAppStats

Background:Lung cancer is the second and third most common cancers found in men and women in Singapore respectively. Literature reveals that survivors of cancer have many concerns and these concerns can linger on for decades.

The aim of this study is to determine the main concerns of cancer survivors at various stages of the cancer survivorship trajectory in order to guide practice.

Materials and Methods:A cross-sectional survey of cancer survivors, defined as an individual from the time of cancer diagnosis through the balance of his or her life, was conducted over a three month period in 2017 at a cancer centre in Singapore. Survivors, who are inflicted with the 6 major types of cancer, aged 21 and older and able to and read and write Chinese and English were asked to evaluate the self-reported concerns based on a questionnaire adapted from the Mayo Clinic Cancer Centre’s Cancer Survivors Survey of Needs. Logistic regression models were fitted to estimate the odds ratios (OR) to assess the association of various variables with the presence of ≥ 1 concerned or very concerned issue among patients. Linear regression models were fitted to identify the variables associated with QOL.

Results:One hundred and sixty nine lung cancer survivors responded to this survey. The top 5 concerns long-term treatment effects (50%), cancer treatment and recurrence risk (50%), followed by fatigue (49%), financial concerns (47%) and loss of strength (44%). Long-term treatment effects and cancer treatment and recurrence risk were amongst the top concerns across the survivorship trajectory. Mean QOL was 6.8 on a scale of 0 – 10. Emotional issue was the only independent predictor for QOL.

Conclusion:Irrespective of the cancer trajectory, survivors of lung cancers have various concerns. Designing patient care delivery that addresses the various concerns identified is critical in assisting them in their coping process.

26 | MLCC 2019

Organiser

Endorsed by

Conference SecretariatWizlink Consulting Pte Ltd2 Venture Drive #16-16Vision ExchangeSingapore 608526Tel: (+65) 6774-5201Fax: (+65) 6774-5203Email: secretariat@mlcc.com.sg

MLCC 2019 | 27

AcknowledgementThe Multidisciplinary Lung Cancer Conference 2019 Organising Committee will like to thank the following for their kind and generous contributions:

PLATINUM

GOLD

SILVER

BRONZE

EXHIBITORS